Clinical Investigation of Medical Devices: Key Requirements
Clinical investigation of a device means the systematic study of an investigational medical device in or on human participants to assess its safety, performance or effectiveness. As per the Medical Device Rules of 2017 (MDR 2017), medical devices are categorised into four categories, depending upon the indications for use and risk level of the device. Medical devices are classified as low risk - Class A; low moderate risk- Class B; moderate high risk- Class C and high risk- Class D.
Clinical investigation is required for the Medical Devices which are new and are not approved by USA, UK, EU, Japan, Australia and Canada countries
No sponsor is allowed to conduct any clinical investigation without approval from CDSCO and institutional ethics committee. Clinical investigation is required for risky medical devices (Class B, Class C and Class D) without predicates. For Class A medical devices, data on clinical investigation may not be required, however in some cases the Central Licencing Authority (CLA), may consider data on clinical investigation necessary.
Clinical investigation may be waived when the investigational medical device is approved by the regulatory authorities of United Kingdom, United States of America, Australia, Canada or Japan and is marketed for at least two years in the above-mentioned country. However, in these cases the following should be fulfilled:
The CLA should be satisfied with the data of safety, performance and pharmacovigilance of the device approved in the respective country.
There should be no evidence or theoretical possibility, on the basis of existing knowledge, of any difference in the behaviour and performance of the device in Indian population.
The applicant would have to furnish an undertaking in writing to conduct post marketing clinical investigation/ performance with the objective of safety and performance of such investigational medical device as per protocol approved by CLA.
Application for grant of permission to conduct clinical investigation for investigational medical device - Form MD-22
An application for grant of permission to conduct clinical investigation for investigational medical device shall be made to the Central Licensing Authority in Form MD-22 by a sponsor and should be accompanied with information specified in the Seventh Schedule of the MDR 2017.
Permission to conduct clinical investigation - Form MD-23
The Central Licensing Authority, if satisfied, that the requirements have been complied with, grants permission to conduct clinical investigation for an investigational medical device in Form MD-23. After grant of permission, clinical investigation can be initiated based on clinical investigation plan duly approved by a registered Ethics Committee. Before enrolling the first participant, clinical investigation needs to be registered with the Clinical Trial Registry of India. The clinical investigation should be mandatorily initiated by enrolling first participant within a period of one year from the date of grant of permission, failing which prior permission from the CLA will be required to initiate clinical investigation.
Types of clinical investigation as per the new Medical Device Regulations, 2017
Pilot Clinical Investigation - Pilot clinical investigation is clinical investigation carried out for the first time in human participants. Pilot clinical investigations are conducted in a small study population (with the disease or condition being studied) to acquire specific essential information about a device before initiating the pivotal clinical investigation. Pilot clinical investigation is an exploratory study which provides an understanding of the performance and safety of a device but cannot provide definitive support for specific mechanistic or therapeutic claims. The objectives of a pilot clinical investigation typically include:
Assessing feasibility (e.g, preliminary device performance)
Exploring eligibility criteria and their practical application for pivotal controlled investigation, ascertaining potential harm (preliminary safety evaluations)
Studying device mechanism
Validating a method for determining an outcome measure
Using a defined device mechanism to validate a surrogate outcome measure
Evaluating the logistics of pivotal investigation for performance
Pivotal clinical investigation - Pivotal clinical investigation is a definitive study/ confirmatory study in which evidence is gathered to support the safety and effectiveness of the medical device for its intended use. Pivotal clinical investigation is conducted in a larger study population (with the disease or condition being studied). For pivotal study, data emerging from pilot clinical investigation is required to be submitted as well. For investigational medical device developed in India, clinical investigation is required to be carried out in India right from Pilot clinical investigation or first in human study and data generated should be submitted. For investigational medical device which does not have a predicate medical device but has been approved for sale or distribution in any country other than India, pivotal studies need to be carried out primarily to generate evidence of safety and effectiveness of the medical device in Indian patients when used as recommended in the prescribing information except in cases of investigational medical device classified under class A which shall be governed on case to case basis by the CLA. Prior to conduct of pivotal clinical investigation in Indian subjects, data from pilot study should be submitted to ensure that the pilot data is in conformity to the data already generated outside the country. Annual status report of each clinical investigation as to whether it is ongoing, completed or terminated should be submitted to CDSCO by the sponsor.
Reference Medical Device Rule. 2017. MINISTRY OF HEALTH AND FAMILY WELFARE. (Department of Health and Family Welfare)